Impact of CD39 and purinergic signalling on the growth and metastasis of colorectal cancer

Despite improvements in prevention and management of colorectal cancer (CRC), uncontrolled tumor growth with metastatic spread to distant organs remains an important clinical concern. Genetic deletion of CD39, the dominant vascular and immune cell ectonucleotidase, has been shown to delay tumor growth and blunt angiogenesis in mouse models of melanoma, lung and colonic malignancy. Here, we tested the influence of CD39 on CRC tumor progression and metastasis by investigating orthotopic transplanted and metastatic cancer models in wild-type BALB/c, human CD39 transgenic and CD39 deficient mice. We also investigated CD39 and P2 receptor expression patterns in human CRC biopsies. Murine CD39 was expressed by endothelium, stromal and mononuclear cells infiltrating the experimental MC-26 tumors. In the primary CRC model, volumes of tumors in the subserosa of the colon and/or rectum did not differ amongst the treatment groups at day 10, albeit these tumors rarely metastasized to the liver. In the dissemination model, MC-26 cell line-derived hepatic metastases grew significantly faster in CD39 over-expressing transgenics, when compared to CD39 deficient mice. Murine P2Y2 was significantly elevated at both mRNA and protein levels, within the larger liver metastases obtained from CD39 transgenic mice where changes in P2X7 levels were also noted. In clinical samples, lower levels of CD39 mRNA in malignant CRC tissues appeared associated with longer duration of survival and could be linked to less invasive tumors. The modulatory effects of CD39 on tumor dissemination and differential levels of CD39, P2Y2 and P2X7 expression in tumors suggest involvement of purinergic signalling in these processes. Our studies also suggest potential roles for purinergic-based therapies in clinical CRC.

Detection of hepatic portal venous gas: its clinical impact and outcome

The clinical impact and outcome of a rare radiographic finding of hepatic portal venous gas (HPVG) as well as the effectiveness of computed tomography (CT), CT scanogram, and conventional radiography in the detection of HPVG were retrospectively analyzed. CT scans, CT scanogram, and plain film radiographs of 11 patients with HPVG were reviewed and compared with their medical records and surgical and pathology reports. Eight of the 11 patients underwent plain film radiographs 1 day before or after the CT scan. HPVG was detected at CT in all 11 patients, on CT scanogram in three (3 of 11, 27.3%), and on plain films in one (one of eight, 12.5%). In nine of 11 patients (81.8%), CT revealed an associated pneumatosis intestinalis. In six of the 11 patients (54.6%), acute mesenteric ischemia was the underlying disease for HPVG. Seven patients (63.6%) underwent emergency exploratory laparotomy. The mortality rate for HPVG alone was 27.3% (3 of 11) and for HPVG related to mesenteric bowel disease 50% (three of six). Acute mesenteric ischemia is the most common cause of HPVG, which continues to have a predictably higher mortality. CT is superior to CT scanograms and radiographs in the detection of HPVG and its underlying diseases and, therefore, should be used as the primary diagnostic tool.

The impact of retrieval processes, age, general achievement level, and test scoring scheme for children's metacognitive monitoring and controlling

This multi-phase study examined the influence of retrieval processes on children’s metacognitive processes in relation to and in interaction with achievement level and age. First, N = 150 9/10- and 11/12-year old high and low achievers watched an educational film and predicted their test performance. Children then solved a cloze test regarding the film content including answerable and unanswerable items and gave confidence judgments to every answer. Finally, children withdrew answers that they believed to be incorrect. All children showed adequate metacognitive processes before and during test taking with 11/12- year-olds outperforming 9/10-year-olds when considering characteristics of on-going retrieval processes. As to the influence of achievement level, high compared to low achievers proved to be more accurate in their metacognitive monitoring and controlling. Results suggest that both cognitive resources (operationalized through achievement level) and mnemonic experience (assessed through age) fuel metacognitive development. Nevertheless, when facing higher demands regarding retrieval processes, experience seems to play the more important role.